BIOCHEMICAL CHARACTERISTICS OF HUMAN PITUITARY SOMATOTROPINOMAS WITH AND WITHOUT GSP MUTATIONS - IN-VITRO CELL-CULTURE STUDIES

Gsp oncogenes are present in about 40% of somatotropinomas. They result in excessive cAMP production and have been proposed to be the cause of increased GH secretion. We have used in vitro cell culture to compare the biochemical characteristics of somatotropinomas with and without gsp oncogenes (gsp-positive and gps-negative tumors, respectively). Of 30 somatotropinomas examined, 10 proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction. The somatostatin anolog, octreotide, powerfully inhibited GH secretion by gsp-negative tumors. Five of 20 gsp-positive and 4 of 10 gsp-positive tumors failed to repond to GHRH, whereas stimulatory effects ranging from 37-500% increases in GH secretion occurred in the remainder. However, strong stimulation (>4-fold) occurred only in 5 of the gsp-negative tumors. The basal phosphatidylinositol turnover rate was elevated in about 25% of gsp-negative somatotropinomas. These results demonstrate similar and highly variable effects of GHRH on both types of somatotropinoma, whereas the absence of gsp oncogenes is often associated with resistance to octreotide. The phosphatidylinositol turnover data suggest that defects within this second messenger system may be present in a subset of somatotropinomas without gsp oncogenes.